Received April 20, 2017; Revision received July 11, 2017
In this work, it was found that the ability of common uncouplers –
carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and
2,4-dinitrophenol (DNP) – to reduce membrane potential of
isolated rat liver mitochondria was diminished in the presence of
millimolar concentrations of the known cytochrome c oxidase
inhibitor – cyanide. In the experiments, mitochondria were
energized by addition of ATP in the presence of rotenone, inhibiting
oxidation of endogenous substrates via respiratory complex I. Cyanide
also reduced the uncoupling effect of FCCP and DNP on mitochondria
energized by succinate in the presence of ferricyanide. Importantly,
cyanide did not alter the protonophoric activity of FCCP and DNP in
artificial bilayer lipid membranes. The causes of the effect of cyanide
on the efficiency of protonophoric uncouplers in mitochondria are
considered in the framework of the suggestion that conformational
changes of membrane proteins could affect the state of lipids in their
vicinity. In particular, changes in local microviscosity and vacuum
permittivity could change the efficiency of protonophore-mediated
translocation.
KEY WORDS: mitochondria, uncoupler, protonophore, oxidative
phosphorylation, mitochondria, respiration, membrane potential